miR-335-5p aggravates type 2 diabetes by inhibiting SLC2A4 expression

Biochem Biophys Res Commun. 2021 Jun 18:558:71-78. doi: 10.1016/j.bbrc.2021.04.011. Epub 2021 Apr 23.

Abstract

Globally, type 2 diabetes (T2D) is the most common chronic disease. It affects approximately 500 million people worldwide. Dysregulation of the solute carrier family 2 member 4 (SLC2A4) gene and miR-335-5p has been associated with T2D progression. However, the mechanisms underlying this dysregulation are unclear. The levels of miR-335-5p and SLC2A4 in blood samples collected from patients with T2D (T2D blood samples) and pancreatic cell lines were measured by Real Time quantitative PCR (RT-qPCR). The relationship between miR-335-5p and SLC2A4 was investigated using a luciferase assay. The role of the miR-335-5p-SLC2A4 axis was detected by CCK8, BrdU, and caspase-3 assays in pancreatic cells treated with 25 mM glucose. Increased miR-335-5p and decreased SLC2A4 expression was observed in both T2D blood samples and pancreatic cell lines. The miR-335-5p mimic markedly suppressed proliferation and elevated apoptosis in glucose-treated pancreatic cells. SLC2A4 overexpression significantly enhanced proliferation but inhibited apoptosis in glucose-treated pancreatic cells. Moreover, miR-335-5p inhibited the expression of SLC2A4 in the pancreatic cells and suppressed the growth of these cells. The data indicated that miR-335-5p targeting of SLC2A4 could hamper the growth of T2D cell model by inhibiting their proliferation and elevating apoptosis. Collectively, our findings implicate miR-335-5p and SLC2A4 as potentially effective therapeutic targets for patients with T2D.

Keywords: Apoptosis; Proliferation; SLC2A4; T2D; miR-335-5p.

MeSH terms

  • Apoptosis / genetics
  • Blood Glucose / metabolism
  • Cell Line
  • Cell Proliferation / genetics
  • Diabetes Mellitus, Type 2 / etiology
  • Diabetes Mellitus, Type 2 / genetics*
  • Diabetes Mellitus, Type 2 / metabolism*
  • Down-Regulation
  • Gene Regulatory Networks
  • Glucose / pharmacology
  • Glucose Transporter Type 4 / antagonists & inhibitors*
  • Glucose Transporter Type 4 / genetics*
  • Glucose Transporter Type 4 / metabolism
  • Healthy Volunteers
  • Humans
  • MicroRNAs / blood
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism*
  • Pancreas / cytology
  • Pancreas / drug effects
  • Pancreas / metabolism
  • Protein Interaction Maps

Substances

  • Blood Glucose
  • Glucose Transporter Type 4
  • MIRN335 microRNA, human
  • MicroRNAs
  • SLC2A4 protein, human
  • Glucose